New research out of Japan is suggesting rheumatoid arthritis (RA) patients who’ve achieved remission might be able to halve their Xeljanz dose.
In fact, the authors of the study, which was published online in Clinical Rheumatology, went as far as to assert that the lower Xeljanz dose could be preferable to complete withdrawal, as it was associated with fewer disease flares.
The study enrolled 100 patients from 2013 to 2017 who had moderate or high scores on the Clinical Disease Activity Index (CDAI), defined as remission (below 2.8), low disease activity (2.8-10), moderate (10-22), and high (above 22). Patients’ mean age was 64, and mean baseline CDAI was 24.5.
All subjects received the 5mg, twice-daily Xeljanz dose for a year. At the end of that period, the patient and their treating physician made the choice to either stop Xeljanz entirely, continue the 5 mg regimen, or cut the dose by half.
When RA flares occurred, those who opted to halve their Xeljanz dose were returned to the full dose, while those who had stopped treatment restarted the full dose. Patients who opted to continue 5mg twice-daily Xeljanz were switched to an alternative treatment in the event of a flare.
A total of 68 patients achieved and maintained remission or low disease activity for a median of 49 weeks and were included in the analysis. At 12 months, the probabilities of flare-free survival in the three groups were 32% in the withdrawal group, 66% among those on the reduced Xeljanz dose, and 94% in the continuation group, respectively.
Of the patients who experienced an RA flared, all but one in the withdrawal group regained disease control within a month of restarting Xeljanz, and all of those in the dose-reduction group regained control within a month of returning to the higher dose.
“These findings suggest that, although immediate withdrawal of tofacitinib may be a feasible strategy in rheumatoid arthritis patients who have entered clinical remission or low disease activity, a dose-reduction strategy seems a better option for most patients,” the study authors wrote.
The U.S. Food & Drug Administration (FDA) approved the 5 mg twice-daily dose of Xeljanz in 2012 to treat adults with RA. Xeljanz XR, an 11 mg, once daily, extended release tablet, was approved in 2016. Both versions received approval for psoriatic arthritis the following year, while a 10 mg twice-daily Xeljanz regimen was approved to treat ulcerative colitis in 2018.
This past July, the FDA ordered Pfizer, Inc. to add a new Black Box Warning to the drug’s label, after the 10 mg twice-daily Xeljanz dose was linked to an increased risk of pulmonary embolism (life-threatening blood clots in the lungs). The agency also restricted Xeljanz to second-line treatment status for ulcerative colitis patients “who are not treated effectively or who experience severe side effects with certain other medicines.”
According to an FDA Drug Safety Communication published on July 26th, doctors should use the lowest effective Xeljanz dose when treating these patients and limit use of the 10mg twice-daily regimen to the shortest duration possible. They should also avoid prescribing Xeljanz to patients already at risk for blood clots.